An immunostimulatory extract based on the medicinal mushroom Agaricus blazei Murill (AbM) has been shown to stimulate mononuclear phagocytes in vitro to produce pro‐inflammatory cytokines, and to protect against lethal peritonitis in mice. The present aim was to study the effect of AbM on release of several cytokines in human whole blood both after stimulation ex vivo and in vivo after oral intake over several days in healthy volunteers. The 17 signal substances examined were; T helper 1 (Th1) cytokines [interleukin (IL)‐2, interferon (IFN)‐γ and IL‐12], T helper 2 cytokines (IL‐4, IL‐5 and IL‐13), pleiotropic (IL‐7, IL‐17), pro‐inflammatory [IL‐1β, IL‐6, tumour necrosis factor (TNF)‐α (mainly produced by Th1 cells)] – and anti‐inflammatory (IL‐10) cytokines, chemokines [IL‐8, macrophage inhibitory protein (MIP)‐1β and monocyte chemoattractant protein (MCP)‐1] and leukocyte growth factors [granulocyte colony‐stimulating factor (G‐CSF), granulocyte/macrophage colony stimulating factor]. After stimulation of whole blood ex vivo with 0.5–5.0% of a mushroom extract, AndoSan™ mainly containing AbM, there was a dose‐dependent increase in all the cytokines studied, ranging from two to 399‐fold (TNF‐α). However, in vivo in the eight volunteers who completed the daily intake (60 ml) of this AbM extract for 12 days, a significant reduction was observed in levels of IL‐1β (97%), TNF‐α (84%), IL‐17 (50%) and IL‐2 (46%). Although not significant, there was a trend towards reduced levels for IL‐8, IFN‐γ and G‐CSF, whilst those of the remaining nine cytokines tested, were unaltered. The discrepant results on cytokine release ex vivo and in vivo may partly be explained by the antioxidant activity of AbM in vivo and limited absorption of its large, complex and bioactive β‐glucans across the intestinal mucosa to the reticuloendothelial system and blood.

The aim was to investigate the antibacterial effect of the biologically active and edible mushroom Agaricus blazei Murill (AbM). A water extract of AbM or PBS control was administered orally before or with challenge to NIH/OlaHsd mice, experimentally infected intraperitoneally with the moderately virulent Streptococcus pneumoniae serotype 6B. End points were bacteraemia and survival rate. The AbM extract, protected against systemic S. pneumoniae 6B infection in the mice. It was most effective when given 24 h before inoculation but did also have protective effects when given together with challenge compared with control. The lack of antibiotic effect on pneumococci in vitro and increased levels of cytokines MIP-2 and TNF-a in the serum of mice receiving AbM extract, indicated that the protective effect of AbM was due to the involvement of the native immune system. This is the first report of anti-infection effects of AbM in vivo. Our results suggest that AbM extract may be useful as additional prophylactic and possibly therapeutic treatment against bacterial and possibly other infections in humans.

An immunomodulatory extract (AndoSan™) based on the medicinal mushroom Agaricus blazei Murill (AbM) has shown to reduce blood cytokine levels in healthy volunteers after 12 days’ ingestion, pointing to an anti‐inflammatory effect. The aim was to study whether AndoSan™ had similar effects on cytokines in patients with ulcerative colitis (UC) and Crohn’s disease (CD). Calprotectin, a marker for inflammatory bowel disease (IBD), was also measured. Patients with CD (n = 11) and with UC (n = 10) consumed 60 ml/day of AndoSan™. Patient blood plasma was harvested before and after 6 h LPS (1 ng/ml) stimulation ex vivo. Plasma and faecal calprotectin levels were analysed using ELISA and 17 cytokines [IL‐2, IFN‐γ, IL‐12 (Th1), IL‐4, IL‐5, IL‐13 (Th2), IL‐7, IL‐17, IL‐1β, IL‐6, TNF‐α, IL‐8, MIP‐1β, MCP‐1, G‐CSF, GM‐CSF and IL‐10] by multiplex assay. After 12 days’ ingestion of AndoSan™, baseline plasma cytokine levels in UC was reduced for MCP‐1 (40%) and in LPS‐stimulated blood for MIP‐1β (78%), IL‐6 (44%), IL‐1β (41%), IL‐8 (30%), G‐CSF (29%), MCP‐1 (18%) and GM‐CSF (17%). There were corresponding reductions in CD: IL‐2 (100%), IL‐17 (55%) and IL‐8 (29%) and for IL‐1β (35%), MIP‐1β (30%), MCP‐1 (22%), IL‐8 (18%), IL‐17 (17%) and G‐CSF (14%), respectively. Baseline concentrations for the 17 cytokines in the UC and CD patient groups were largely similar. Faecal calprotectin was reduced in the UC group. Ingestion of an AbM‐based medicinal mushroom by patients with IBD resulted in interesting anti‐inflammatory effects as demonstrated by declined levels of pathogenic cytokines in blood and calprotectin in faeces.

Since the 1980s, medicinal effects have been documented in scientific studies with the related Basidiomycota mushrooms Agaricus blazei Murill (AbM), Hericium erinaceus (HE) and Grifola frondosa (GF) from Brazilian and Eastern traditional medicine. Special focus has been on their antitumor effects, but the mushrooms’ anti-inflammatory and antiallergic properties have also been investigated. The antitumor mechanisms were either direct tumor attack, e.g., apoptosis and metastatic suppression, or indirect defense, e.g., inhibited tumor neovascularization and T helper cell (Th) 1 immune response. The anti-inflammatory mechanisms were a reduction in proinflammatory cytokines, oxidative stress and changed gut microbiota, and the antiallergic mechanism was amelioration of a skewed Th1/Th2 balance. Since a predominant Th2 milieu is also found in cancer, which quite often is caused by a local chronic inflammation, the three conditions—tumor, inflammation and allergy—seem to be linked. Further mechanisms for HE were increased nerve and beneficial gut microbiota growth, and oxidative stress regulation. The medicinal mushrooms AbM, HE and GF appear to be safe, and can, in fact, increase longevity in animal models, possibly due to reduced tumorigenesis and oxidation. This article reviews preclinical and clinical findings with these mushrooms and the mechanisms behind them.